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This study was conducted to determine the antibacterial effect of crude and fractionated extracts of leaves of Vernonia amygdalina against multiple antibiotic resistant bacteria isolate from wounds. The bacteria isolates obtained are: Staphylococcus aureus, Escherichia coli, Pseudomonas aeuroginosa, Klebsiella pneumoniae, Proteus mirabilis and Streptococcus pyogene; they were confirmed standard microbiological techniques. Extracts were prepared from the leaf of the plant using ethanol, chloroform, cold water and hot water. The antibacterial activities of the crude extracts were assayed using the agar well diffusion methods. Multiple antibiotic resistant of the isolates was confirmed in the six (6) isolates. The phytochemical screening revealed the presence of alkaloids, phenols and saponins. All the extract showed varying degrees of activities depending on the extract concentration and the extract solvent. Generally, ethanol rated best as the extraction solvent which was able to inhibit all isolates except K. pneumoniae and P. mirabilis, and inhibits S. aureus at 50 mg/ml with zones 6.997±0.003. The antibacterial efficacy of the extract increases with a corresponding increase in the extract concentration. The MBC values ranged from 50 - 400 mg/mL for all the extraction solvent, and this is very important for people who depend on the plant for their health care needs. Fra 1, 6, and 10 of the column fractions were able to inhibit with 8.997 ± 0.008 mm, 8.993 ± 0.012 mm and 9.007 ± 0.000 mm respectively. The functional groups are Alkene, alkane group, alkyl halides, N-H bend of amides and Alcohol. The leaf of Vernonia amgydalina can be used as a raw material for the production of new antibiotic to control multiple resistant bacteria.